The loss of bone in periodontal disease is largely the result of increased osteoclastic activity. While substantial new insight has been gained in identifying the factors involved in evoking this increased activity, the fundamental process of bone resorption remains incompletely understood. Much of this confusion reflects limitations inherent in most existing techniques for analyzing the resorptive process. In our original application, we proposed to explore new and less equivocal approaches to bone resorption. Our efforts have lead to the development of assay systems which employ essentially pure populations of resorptive cells (monocytes, macrophages and, more recently, multinucleated macrophages). These assays permit kinetic and quantitative analysis of two of the major events in the bone resorption sequence; the attachment of resorptive cells to the bone surface and bone matrix degradation. With these techniques in hand, along with some recently acquired biochemical skills, we are now in a position to address some of the fundamental issues of bone resorption. Specifically, we propose to: 1) examine the mechanisms by which resorptive cells recognize and bind to bone; 2) establish the temporal relationships between the binding process and onset of bone resorption; 3) determine the role of collagenase, other neutral proteinases and selected acid hydrolases in bone matrix degradation; 4) explore the functional relationship between the acquisition of multiple nuclei (as in osteoclastic development) and increased resorptive efficiency.